New-Device Angioplasty in Women: Clinical Outcome and Predictors in a 7,372-Patient Registry
Lansky, Alexandra J.; Mehran, Roxana; Dangas, George; Desai, Kartik; Costantini-Ortiz, Costantino; Cristea, Ecaterina; New, Gishel; Negoita, Manuela; Stone, Gregg W.; Leon, Martin B.
From the Cardiac Catheterization Laboratory and the Women’s Cardiac Health Initiative, Lenox Hill Hospital, New York City, NY.
Address correspondence to: Alexandra J. Lansky, Director, Angiographic Core Laboratory, and Women’s Cardiac Health Initiative, 55 East 59th Street, 6th Floor, New York, NY 10022; E-mail: email@example.com
This study was supported in part by the Cardiovascular Research Foundation, New York, NY.
Background. Female gender has been identified as an independent predictor of early complications and mortality after conventional balloon angioplasty. To gain insight into the outcome of women after new-device angioplasty, we reviewed the early and late clinical outcome of 7,372 patients undergoing new-device angioplasty between 1991 and 1996 at the Washington Hospital Center.
Methods. Patients (2,077 women and 5,295 men) with native coronary artery (82.5%) or saphenous vein graft lesions undergoing new-device angioplasty were included in the study. In-hospital and 1-year major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization (TLR), were recorded and compared on the basis of gender. Multivariable logistic regression analysis was performed to identify predictors of in-hospital and late mortality, follow-up MACE, and TLR.
Results. Women had more baseline comorbid risk factors and smaller reference vessel size compared with men. Women had a higher in-hospital cardiac mortality (1.39%vs 0.66%, P = 0.002), TLR (2.78%vs 1.81%, P = 0.008), and congestive heart failure (4.18%vs 2.29%, P < 0.001) compared with men. Overall in-hospital MACE tended to be higher among women (4.2%vs 3.3%, P = 0.074). Women had a higher 1-year mortality rate (4.39%vs 3.26%, P = 0.018), but a lower follow-up TLR (15.0%vs 18.1%, P = 0.001) and a lower overall MACE rate (29.2%vs 32.7%, P = 0.007) compared with men. Female gender was an independent predictor of in-hospital mortality (odds ratio 2.28, P = 0.02), but not late mortality.
Conclusions. Although female gender appears to carry an inherent risk of in-hospital mortality after new-device angioplasty, the procedural success and mortality rates are favorable compared with those associated with balloon angioplasty series. The long-term clinical outcome of women after new-device angioplasty is excellent. The use of new devices is a safe and effective alternative strategy for the treatment of women with ischemic coronary artery disease. Device-specific outcomes, including stents, will require further evaluation.
In the 1985 National Heart, Lung, and Blood Institute (NHLBI) percutaneous transluminal coronary angioplasty (PTCA) Registry, female gender was identified as an independent predictor of early complications and mortality after angioplasty. 1 In contemporary series, women undergoing balloon angioplasty continue to have a higher in-hospital mortality than men despite marked improvements in procedural success. 2–4 Gender differences of in-hospital outcomes may be influencing hospitalization costs, 5 and may be contributing in part to the frequent referral bias and the less aggressive diagnostic evaluation of women with coronary syndromes. 6–10 As angioplasty techniques evolve, the outcome of women undergoing coronary intervention should be redefined in an effort to change referral patterns of women with coronary artery disease.
The purpose of this study was to define gender differences of in-hospital and late clinical outcomes, and to identify predictors of in-hospital and 1-year clinical events in a contemporary registry of 7,372 patients undergoing “new-device” coronary angioplasty.
From July 1991 through July 1996, a consecutive series of patients providing informed consent were included in this registry if they had evidence of myocardial ischemia or a native or saphenous vein graft (SVG) lesion treated with new-device angioplasty, including directional, rotational, or extraction atherectomy; excimer laser; newer-generation balloon angioplasty; or stenting. Angioplasty with new devices or stents was performed using standard techniques, including premedication with aspirin 325 mg, and procedural heparin to achieve an activated clotting time >300 seconds. Before 1994, patients undergoing intracoronary stenting received aggressive anticoagulation with dextran, aspirin, heparin, and coumadin; beginning in 1994, a reduced anticoagulation strategy included daily aspirin 325 mg indefinitely and ticlopidine 250 mg twice daily for 4 weeks after the procedure was adopted.
Data Collection and Endpoints
The hospital records of all patients were reviewed to identify baseline characteristics and postprocedural complications. Unstable angina was defined as recent acceleration of symptoms and included rest pain associated with electrocardiogram changes. Myocardial infarction was defined as a rise in total creatinine kinase more than two times normal with a positive MB fraction in association with any of the following criteria: (1) ischemic chest pain lasting more than 30 minutes, (2) a new two-step Minnesota Code Q-wave, (3) persistent ST- or T-wave changes, or (4) a new left bundle branch block. All procedural cine-angiograms were obtained using standard acquisition guidelines, and a subgroup of 74% of the angiograms (N = 1404 for women, N = 4025 for men) were analyzed by an independent Angiographic Core Laboratory (Cardiovascular Research Foundation, New York, NY). Standard morphologic criteria were used to characterize baseline lesion complexity 11 and to identify the occurrence of angiographic complications. 12 Quantitative angiographic analysis was performed using the ArTrek system (Quinton, Inc, Bothell, WA). 13 The mean reference diameter (RD) and the minimal lumen diameter (MLD) were used to calculate the percentage diameter stenosis [(1 − MLD/RD) × 100] stenosis. Angiographic success was defined as a final diameter stenosis <50% and a >20% improvement in diameter stenosis. Procedure success was defined as a <50% final diameter stenosis and the absence of death, Q-wave myocardial infarction, emergency, or urgent bypass surgery. After hospital discharge, patients were prospectively traced for 12 months to monitor the occurrence of major adverse cardiac events (MACE), which included death, Q-wave myocardial infarction, and target lesion revascularization (TLR) by either repeat coronary angioplasty of the target site or coronary bypass surgery.
Continuous variables are presented as mean ± standard deviation, and dichotomous variables are presented as frequencies. Differences between continuous variables were analyzed using the Mann-Whitney U test, and differences in frequencies among dichotomous variables were determined with the chi-square or Fisher’s exact test. Multivariable logistic analyses were performed to identify clinical and angiographic predictors of (1) in-hospital mortality, (2) 1-year MACE, (3) death, and (4) TLR. Variables included in the model were gender, body surface area, diabetes, history of prior myocardial infarction or PTCA, unstable angina, age, reference vessel size, lesion length, and final minimal lumen diameter. A two-tailed P value <0.05 was considered significant.
Patient, Lesion, and Procedural Characteristics
A total of 2,077 women and 5,295 consecutive men with 12,272 native coronary (82.5%) and saphenous vein graft (17.5%) lesions underwent new-device angioplasty or stenting at the Washington Hospital Center. New devices included directional (13.9%), rotational (23.9%), and extraction (2.3%) atherectomy; eximer laser angioplasty (9.8%); stenting (32.7%); and “stand-alone” newer-generation balloon angioplasty (17.4%). Overall, women had more comorbid cardiac risk factors compared with men, and a higher left ventricular ejection fraction (Table 1). Angiographic analysis was performed on a consecutive subset of 5,428 patients. Although vessel distributions were similar, men had longer (9.23 ± 7.05 vs 8.80 ± 6.70 mm, P = 0.026) and more ulcerated and thrombus-containing lesions, and more SVG degeneration, whereas women had more calcified lesions (Table 2). Compared with men, women had smaller reference vessel size (2.66 ± 0.60 vs 2.81 ± 0.64 mm, P = 0.0008) (Table 2).
In-Hospital Clinical Outcome
The overall angiographic success rate (>97%) and procedural success rate (>92%) were excellent for both men and women. Angiographic complications were infrequent; however, men had more distal embolization, whereas women had more coronary perforations. Women had higher in-hospital target lesion revascularization, more congestive heart failure despite a higher left ventricular ejection fraction, and more major vascular complications as compared with men (Table 3). Importantly, women had a higher in-hospital mortality than men (1.39%vs 0.66%;P = 0.002). By multivariable logistic regression analysis, female gender was an independent predictor of in-hospital mortality (Table 4).
Clinical Outcomes at Follow-Up
At 1-year follow-up, women had a higher mortality than men (4.39%vs 3.26%, P = 0.018), whereas men underwent more target lesion revascularization (18.2%vs 15.0%, P = 0.001) (Table 3). By multivariable logistic regression analysis, female gender was not an independent predictor of 1-year mortality. Male gender predicted the need for TLR (odds ratio = 1.54, P = 0.0001) and MACE (odds ratio = 1.53, P = 0.0001) at 1-year follow-up (Table 4).
This contemporary series of 7,372 consecutive patients undergoing new-device angioplasty, including the newer-generation balloons, demonstrates significant gender differences in clinical outcomes. Despite similar angiographic and procedural success rates, women have higher periprocedural mortality and tend to have more overall complications than men. Gender differences in baseline characteristics may be contributing to the worse outcome among women. However, female gender remains an independent predictor of in-hospital mortality after new-device angioplasty in this registry. Although women had a higher mortality than men at 1-year follow-up, by multivariate analysis, female gender was not associated with long-term mortality in our registry.
Gender Differences in Acute Outcome after New-Device Angioplasty
The greatest impact of new devices including the newer-generation balloons has been the overall improvement in procedural and angiographic success rates. With the original balloon angioplasty devices available before 1985, the range of procedure success was 60–70% and improved to 80–90% after 1985. 1,3,14–16 In the current study, procedure success was further improved with new-device angioplasty in both men and women (>92%). Although women continue to have a higher mortality than men, in-hospital mortality rates in women undergoing new-device angioplasty (<1.5%) remain comparable and possibly lower than previously reported rates (up to 4.1%) associated with balloon angioplasty alone. 1,3,15–17
Clinical factors are known to contribute to the higher morbidity and mortality in women after revascularization procedures; however, adjusting for age and other comorbid conditions does not always completely eliminate the differences in outcomes. 2–4,15 Differences in vessel size and body surface area (BSA) have long been held to be important factors contributing to the apparent gender discrepancy in outcome. 18 In the NHLBI PTCA registries, men of short stature had rates of mortality similar to those of women. 1,3 In a series of 5,000 angioplasty patients from the Cleveland Clinic, women’s increased in-hospital mortality (1.1%vs 0.3%, P = 0.001) was no longer significant after correcting for differences in BSA. 17 The higher mortality associated with a smaller BSA is presumably due to higher procedural complications such as dissections and perforations. Specific cause and effect have yet to be elucidated.
As in most prior angiographic reports, the women in this study had smaller vessel size than men (2.66 ± 0.60 vs 2.81 ± 0.64 mm, P = 0.0008); however, in contrast to other angiographic studies in which differences in mortality were abolished after correcting for differences in body surface area or vessel caliber, 19,20 the current study still identified women to have an inherent risk of mortality after coronary intervention. Whether women have an inherent biological risk or whether the excess mortality is the result of other procedure-related factors that were not specifically measured is not clear. For example, the higher incidence of congestive heart failure in the context of a higher left ventricular ejection fraction suggests more diastolic dysfunction among women. The implications of diastolic dysfunction and congestive heart failure on postprocedure complications including mortality, and the impact of the contrast load, are not well defined. Ongoing studies are currently evaluating device-specific outcomes in women to determine whether the specific device selection affects mortality.
Vascular complications were more frequent in women likely as a result of the aggressive anticoagulation regimen and the infrequent use of weight-adjusted heparin dosing during the time period of the study. In addition, sheath size has rarely been adjusted during intervention of female patients despite their smaller body size. This practice has now evolved with use of smaller sheath sizes as a result of the smaller profile of newer third- and fourth-generation devices. With the advent of adjunctive pharmacology with IIb/IIIa inhibitors, weight-adjusted heparin is now a more common practice. Whether these changes in practice have made an impact on vascular complication rates requires further study.
Gender Differences in Long-Term Outcome after New-Device Angioplasty
Paradoxically, although small vessel size and small postprocedural lumen diameters are typically associated with higher restenosis rates at follow-up after balloon or new-device angioplasty, 21–25 women are consistently reported to have target vessel revascularization rates that are similar to or lower than those of men. 3,17,26,27 In this series, the 1-year TLR and major adverse clinical event rates were lower in women, and male gender was actually an independent risk for follow-up events. Although gender differences in restenosis rates have not been well defined, lower follow-up revascularization rates among women have been reported in previous angioplasty series. 1,16,26 This may reflect a true reduction in the need for repeat revascularization in women or a potential referral bias, in which women are less likely, because of differences in symptoms or noninvasive test results or other reasons, to be referred or admitted for subsequent revascularization.
The mortality at 1 year after new-device angioplasty was higher for women than for men (4.39%vs 3.26%, P = 0.018); independent predictors included diabetes mellitus, unstable angina at the time of intervention, and prior myocardial infarction, but not gender. The late outcome after new-device angioplasty in this registry compares favorably with prior reports in patients undergoing balloon angioplasty (3.7–10.8%). 2,3,15
Despite the large number of patients included, this study has inherent limitations associated with a retrospective analysis. In addition, this analysis does not provide a device-specific evaluation. Although we report the overall impact of new devices on gender-based outcome, the results are not generalizable to a specific angioplasty device. Although the study evaluates outcomes with new devices, it does not necessarily reflect current (2002) practice patterns, in which a majority (>70%) of coronary interventions now include the use of stents and increasing use of adjunctive antiplatelet pharmacotherapy with glycoprotein IIB/IIIA inhibitors.
Clinical Implications and Conclusions
Women undergoing new-device angioplasty have more comorbid disease, and a slightly but significantly higher in-hospital mortality and complication rate, compared with men. However, compared with balloon angioplasty series, the procedural success has increased and mortality has decreased with the availability of new devices. Late clinical outcomes of women with new-device angioplasty are favorable compared with historical balloon angioplasty series. Despite the slight increase of in-hospital cardiac mortality in women, new-device angioplasty is a safe and effective treatment strategy for women with symptomatic coronary artery disease. With the increasing use of intracoronary stents, reassessing women’s procedural risk after stenting is warranted.
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